As used herein, the terms “mass analyser” or “mass detector” or “mass spectrometer” refer to an apparatus, device or instrument that produces a signal or result based on a mass to charge ratio of analyte ions. Mass analysers may take several common forms, such as, by way of example, without limitation, quadrupole mass filters, ion trap mass analyzers, magnetic sector mass analyzers, time-of-flight mass analyzers, ion-cyclotron resonance (FTMS) analyzers, and Kingdon trap analysers.
Mass spectrometers used for the analysis of biomolecules usually employ atmospheric pressure ionization (API) sources. API sources suitable for the analysis of solutions include electrospray (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI), and pneumatically and/or thermally assisted electrospray sources. API is also used with techniques such as matrix assisted laser desorption (MALDI), desorption electrospray ionization (DESI), desorption ionization on silicon (DIOS), and “DART” (direct analysis in real time).
The mass analysis of ions is usually carried out at sub-atmospheric pressures, so that all API techniques require an interface for transmitting ions from the source into a region of relatively high vacuum, usually via one or more evacuated chambers. Ion transmission devices, typically comprising sets of elongated rods or apertured disks to which alternating potentials are applied, are typically provided in chambers where the pressure is sufficiently low for them to be effective. However, most interfaces between API sources and a mass analyzer also comprise a vacuum chamber without an ion transmission device through which the ions have to pass. The following discussion relates particularly to electrospray API sources, but it will be understood that the interfaces described are equally applicable to the other types of API sources listed above, or indeed to any ionization source which generates a plume or spray of ions in a region of relatively high, or atmospheric pressure.
Electrospray ion sources generate an aerosol comprising electrically charged droplets from a solution (often the eluent from a liquid chromatograph) by means of an electrical field applied between a counter electrode and a capillary tube through which the solution flows. The charged droplets may comprise ions characteristic of a sample dissolved in the solution. These charged droplets are at least partially desolvated through contact with gas molecules present in the source, which is usually maintained at atmospheric pressure. Desolvation may be assisted by suitably directing one or more flows of gas in relation to the electrosprayed aerosol, and/or by heating the gas and/or the capillary tube. Replacing the capillary tube with a pneumatic nebulizer (usually a concentric flow nebulizer) may further improve desolvation and additionally may increase the maximum solution flow rate which the source can accept. When a nebulizer is used, the electrospray ionization process may be replaced (or assisted) by a corona discharge (APCI) or a beam of photons (APPI), so that an electrical field between the nebulizer and the capillary may not be necessary.
Whatever processes of ionization and desolvation are used, the ions generated in the atmospheric pressure portion of the source must pass through an interface between the source and the vacuum system of the spectrometer. It is desirable that the interface transmit as many as possible of the ions generated in the aerosol, complete their desolvation without causing losses (for example, by thermal decomposition), and simultaneously separate and remove most of the inert gas and solvent so that the pressure in the mass analyzer is maintained low enough for its proper operation. These requirements are not easily met and many different source and interface designs have been proposed.
The geometrical arrangement of the API source, with respect to the relative orientations of the aerosol and the entrance aperture of the interface, may influence the sensitivity of a mass detector. The structure of the aperture and type of interface have also been found to influence performance.
The interface is subjected to a stream of sample and, due to the small orifices and passageways, can accumulate deposits. It is desirable to have an interface that can be readily removed, cleaned or replaced with an alternative interface.
As used herein, the term “high pressure” refers to relative pressure compared to parts of a mass analyser that operate at low pressures approaching vacuum conditions. The term includes, but is not limited to, “atmospheric pressure”. As used herein, “atmospheric pressure” includes the operation of a device in the presence of significant quantities of gas, perhaps with pressures several hundred torr either side of atmospheric pressure itself. The term is generally used in the art to distinguish a type of device and ionization source at or about atmospheric pressures from those that operate under high or medium vacuum, for example, an electron impact or chemical ionization source.
The terms “charged particles” and “ions” are meant to include singly- and multiply-charged ions, solvated and or desolvated ions, adduct ions, and cluster ions, and the like. Ions and/or charged particles are typically formed from a sample in an ionization source operating at atmospheric pressure (as defined above) and potentially carry one or more analytes of interest, other carrier or sample molecules, solvents and gases, charged droplets of solvent and the like.